1.Clinical Efficacy of Gandou Fumu Decoction in Treating Hepatolenticular Degeneration with Liver Fibrosis of Liver-kidney Deficiency and Phlegm-blood Stasis Syndrome
Pingping YANG ; Meixia WANG ; Changchang CAO ; Zhuang TAO ; Jiang DU ; Yun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):182-191
ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction (GDFMD) in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome, thereby providing evidence-based medical evidence for the treatment of Wilson's disease (WD)-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1, 2023, to October 1, 2024. Participants were divided into a control group and an observation group, with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate (DMPS). On this basis, the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days, for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses, respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement (LSM), liver serological markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅳ collagen (C-Ⅳ), laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP), and hyaluronic acid (HA)], fibrosis index based on 4 factors (FIB-4), AST to platelet ratio index (APRI), unified Wilson's disease rating scale part Ⅱ (UWDRS-Ⅱ), traditional Chinese medicine (TCM) syndrome score, 24-hour urinary copper, and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment, LSM levels decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses, and the improvement of LSM levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the levels of HA, LN, PⅢNP, and C-Ⅳ decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses, and the levels of HA, LN, and PⅢNP were more obvious (P<0.05). After four treatment courses in the observation group, the levels of HA, LN, PⅢNP, and C-Ⅳ were improved more significantly (P<0.05). Compared with those before treatment, ALT and AST levels decreased in both groups after two and four treatment courses (P<0.05). Compared with the control group after treatment, there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses, and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, APRI score and FIB-4 index level decreased in both groups after two and four treatment courses (P<0.05). Compared with those in control group after treatment, there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses, and the APRI score in the observation group was more obvious after four treatment courses (P<0.05), with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment, the levels of TCM syndrome scores decreased in both groups after two and four treatment courses (P<0.05). Compared with that of the control group after treatment, there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses, and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously, and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses (P<0.05). Compared with those of the control group after treatment, there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses, and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious (P<0.05). Compared with those before treatment, the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses (P<0.05). Compared with those in the control group after treatment, the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses (P<0.01). After two treatment courses, the 24-h urine copper level in the observation group showed a gradual decreasing trend, although it was higher than that before treatment. After four treatment courses, the control group had an improvement rate of 91.43%, an effective rate of 34.29%, and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%, an effective rate of 71.43%, and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group (P<0.05). Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy, and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety, which is worthy of clinical popularization and application.
2.Clinical Efficacy of Gandou Fumu Decoction in Treating Hepatolenticular Degeneration with Liver Fibrosis of Liver-kidney Deficiency and Phlegm-blood Stasis Syndrome
Pingping YANG ; Meixia WANG ; Changchang CAO ; Zhuang TAO ; Jiang DU ; Yun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):182-191
ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction (GDFMD) in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome, thereby providing evidence-based medical evidence for the treatment of Wilson's disease (WD)-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1, 2023, to October 1, 2024. Participants were divided into a control group and an observation group, with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate (DMPS). On this basis, the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days, for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses, respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement (LSM), liver serological markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅳ collagen (C-Ⅳ), laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP), and hyaluronic acid (HA)], fibrosis index based on 4 factors (FIB-4), AST to platelet ratio index (APRI), unified Wilson's disease rating scale part Ⅱ (UWDRS-Ⅱ), traditional Chinese medicine (TCM) syndrome score, 24-hour urinary copper, and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment, LSM levels decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses, and the improvement of LSM levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the levels of HA, LN, PⅢNP, and C-Ⅳ decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses, and the levels of HA, LN, and PⅢNP were more obvious (P<0.05). After four treatment courses in the observation group, the levels of HA, LN, PⅢNP, and C-Ⅳ were improved more significantly (P<0.05). Compared with those before treatment, ALT and AST levels decreased in both groups after two and four treatment courses (P<0.05). Compared with the control group after treatment, there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses, and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, APRI score and FIB-4 index level decreased in both groups after two and four treatment courses (P<0.05). Compared with those in control group after treatment, there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses, and the APRI score in the observation group was more obvious after four treatment courses (P<0.05), with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment, the levels of TCM syndrome scores decreased in both groups after two and four treatment courses (P<0.05). Compared with that of the control group after treatment, there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses, and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously, and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses (P<0.05). Compared with those of the control group after treatment, there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses, and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious (P<0.05). Compared with those before treatment, the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses (P<0.05). Compared with those in the control group after treatment, the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses (P<0.01). After two treatment courses, the 24-h urine copper level in the observation group showed a gradual decreasing trend, although it was higher than that before treatment. After four treatment courses, the control group had an improvement rate of 91.43%, an effective rate of 34.29%, and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%, an effective rate of 71.43%, and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group (P<0.05). Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy, and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety, which is worthy of clinical popularization and application.
3.Traditional Chinese medicine syndrome and syndrome differentiation-based treatment of Wilson disease
Wenjie HAO ; Wenming YANG ; Ting CHENG ; Hailin JIANG ; Han WANG ; Meixia WANG
Journal of Clinical Hepatology 2026;42(3):522-528
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, and decoppering therapy and symptomatic treatment are the main Western medicine therapies for WD. This article systematically reviews the understanding of the etiology and pathogenesis of WD in traditional Chinese medicine (TCM) and points out that abnormal natural endowment is the core etiology and pathogenesis of WD, with internal accumulation of copper toxicity as the manifestation, liver/spleen/kidney dysfunction as the root cause, and intermingled “toxin, stasis, phlegm, and deficiency” as the key pathogenesis. Literature research and clinical observation are conducted to summarize the common TCM syndromes of WD, including stagnation of liver Qi, internal retention of damp-heat, phlegm-stasis-heat accumulation syndrome, liver-kidney Yin deficiency syndrome, spleen-kidney Yang deficiency, and syndrome of deficiency damage and phlegm stasis. This article proposes the corresponding therapies and representative prescriptions for each syndrome and discusses the advantages of treatment by stage and integrated traditional Chinese and Western medicine therapy. This article aims to provide a systematic reference for the syndrome differentiation-based treatment of WD in clinical practice of TCM, thereby giving full play to the advantages of TCM in the treatment of this disease.
4.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
5.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
6.Preliminary establishment of comprehensive risk assessment indicator system for occupational health based on Delphi method and analytic hierarchy process
Weiqi SUN ; Meixia LIU ; Tongning GAO ; Yuqi CHEN ; Yan YIN
Journal of Environmental and Occupational Medicine 2026;43(6):754-761
Background Occupational health risk assessment is the foundation of safeguarding workers' occupational health. However, traditional assessment methods often fail to adequately account for health effects and enterprise-specific characteristics, limiting their comprehensive evaluation capabilities. Additionally, these methods suffer from inconsistent standards, narrow application scopes, insufficient hazard sub-categorization, and indicator systems that poorly support informatization and digital transformation. To address these gaps, this study proposes methodological innovations focusing on the assessment indicator system. Objective To construct a systematic, generalizable, and practical occupational health comprehensive risk assessment indicator system by leveraging occupational health practices and surveillance big data from Shanghai. Methods Initial system indicators were extrated through literature review. Subsequently, expert interviews and group discussions, combined with occupational health surveillance big data, were used to refine these indicators, forming a candidate pool covering two major dimensions: risk factor characteristics and enterprise characteristics. The Delphi method was applied to evaluate and screen the indicators, while the analytic hierarchy process (AHP) was used to construct a hierarchical model and determine indicator weights. Results A total of 76 articles were reviewed, identifying 25 candidate indicators. After two rounds of Delphi expert consultation, 8 primary indicators (e.g. hazard characteristics, exposure characteristics, health effects, industry characteristics, management characteristics, protective features, adverse events, and uncertainty) and 17 secondary indicators (hazard factor characteristics, exposure levels, number of people exposed, number of factor exposure, special physical exam indicators, suspected occupational diseases, occupational diseases, industry categories, organizational management, hazard reporting, occupational health training, hazard factor testing, occupational health exams, protective facilities, personal protective equipment, administrative penalties, and data quality) were finalized. The expert response rate was 100%, and the expert authority coefficient was 0.86. The Kendall's W coefficients for importance and accessibility scores across the two consultation rounds were 0.41, 0.40 and 0.41, 0.50. A hierarchical model targeting the comprehensive occupational health risk index was constructed, comprising two major elements and three levels of indicators. AHP was applied to calculate the weights, with all judgment matrices demonstrating satisfactory consistency (consistency ratio < 0.1). Conclusion By integrating risk factor profiles with enterprise-specific characteristics via the Delphi-AHP approach, a robust occupational health comprehensive risk assessment indicator system is established. This system provides a practical framework for digitized occupational health management, though further empirical validation in real-world settings is warranted.
7.Predicting Hepatic Fibrosis Risk in Wilson's Disease: Development and Validation of Prognostic Model Integrating TCM Syndromes and Modern Biomarkers
Jiafeng ZHOU ; Meixia WANG ; Zhuang TAO ; Shuai KANG ; Gang WANG ; Rui WANG ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):197-207
ObjectiveTo analyze the influencing factors of hepatic fibrosis in patients with Wilson's disease (WD) and to develop and validate a predictive model for hepatic fibrosis in WD that integrates traditional Chinese medicine (TCM) syndromes and modern biomarkers, thus providing a basis for early identification of high-risk populations and medical intervention. MethodsThe clinical data of 220 WD patients diagnosed in the Department of Encephalopathy, The First Affiliated Hospital of Anhui University of Chinese Medicine between January 2010 and December 2024 were retrospectively collected. Through a random number table, patients were assigned into a training set (154 patients) and a validation set (66 patients) in a 7∶3 ratio. Univariate COX regression, LASSO regression analysis, and multivariate COX regression analysis were performed to identify independent influencing factors for hepatic fibrosis in WD patients, and a clinical prediction model was established based on these factors. The discrimination, calibration, and clinical utility of the model were evaluated based on the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA), respectively. ResultsA total of 220 patients were included. The syndrome of combined phlegm and stasis, triglycerides (TG), laminin (LN), and male gender were identified as independent risk factors for hepatic fibrosis in WD patients, while TCM intervention and high-density lipoprotein cholesterol (HDL-C) were protective factors. The C-index indicated excellent discriminative ability (training set: 3-year AUC=0.908, 5-year AUC=0.869, 7-year AUC=0.829; validation set: 3-year AUC= 0.898, 5-year AUC=0.780, 7-year AUC=0.743). Calibration curves showed good consistency. DCA demonstrated the clinical net benefit probabilities across different risk thresholds at various time points. ConclusionThe predictive model established in this study has high accuracy and can be conveniently used for the early identification and risk prediction of hepatic fibrosis in patients with WD.
8.Gantou Fumu Decoction Inhibits Hepatic Stellate Cell Activation by Regulating Nrf2/ARE Signaling Pathway
Wangsheng HE ; Yanping ZHU ; Shizhen LONG ; Mengmeng LI ; Wenming YANG ; Han WANG ; Meixia WANG ; Ting DONG ; Shupei JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(23):105-115
ObjectiveTo explore the mechanism through which Gantou Fumu decoction (GDFMT)-containing serum inhibits the activation of hepatic stellate cells. MethodsSerum pharmacology techniques were employed to prepare GDFMT-containing serum samples. Rat hepatic stellate cells (HSCT6) were randomly allocated into three groups: Control, penicillamine (90 mg·kg-1), and GDFMT (6.8 g·kg-1). Cell viability was assessed by the cell counting kti-8 (CCK-8) assay, intracellular ROS levels were determined by flow cytometry using the DCFH‑DA fluorescent probe and while extracellular collagen Ⅰ (ColⅠ) levels were quantified via enzyme linked immunosorbent assay (ELISA). Intracellular α-smooth muscle actin (α-SMA) expression was visualized through immunofluorescence staining. Real-time polymerase chain reaction(Real-time PCR) and Western blot were performed to evaluate alterations in the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), glutamate cysteine ligase, catalytic (GCLC), glutamate-cysteine ligase, modifier subunit (GCLM), Kelch-like ECH-associated protein 1 (Keap1), NAD(P)H:Quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1). Genetic knockdown of Nrf2 was achieved through small interfering (siRNA) transfection to validate pathway specificity. ResultsCCK-8 data indicated that under the selected experimental conditions, culturing HSCT6 cells with 10% (volume fraction) GDFMT-containing serum for 48 h demonstrated equivalent effect in inhibiting HSCT6 cell proliferation compared with culturing HSCT6 cells with 10% (volume fraction) penicillamine-containing serum for 36 h, with no statistically significant difference between the two groups. After treatment of HSCT6 cells with siRNA-mediated Nrf2 gene transfection technique, the inhibitory effect of GDFMT on the activation process of HSCT6 cells was significantly weakened. After HSCT6 cells were cultured with GDFMT-containing serum for 48 h, the flow cytometry with a fluorescence probe showed that the content of reactive oxygen species (ROS) in the cells was significantly reduced. After the expression level of the Nrf2 gene in HSCT6 cells was knocked down by siRNA transfection, the content of ROS increased (P<0.01), indicating that GDFMT significantly reduced the ROS level in activated HSCT6 cells, and this effect strictly depended on the integrity of the Nrf2 pathway. Quantitative analysis by ELISA showed that the synthesis of ColⅠ in the HSCT6 cell culture system treated with GDFMT-containing serum for 48 h was lower than that in the control group (P<0.01). After the Nrf2 gene level of HSCT6 cells was knocked down by siRNA transfection, the ColⅠ concentration in the culture supernatant increased (P<0.01). The results of α-SMA detection by IF method showed that compared with the normal group, GDFMT-containing serum reduced the expression of α-SMA (P<0.01) and the protein level of α-SMA in HSCT6 cells was increased (P<0.01) after siRNA-mediated Nrf2 silencing, suggesting that Nrf2 signaling pathway may be involved in regulating the phenotypic transformation process of the cells. Real-time PCR and Western blot results showed that GDFMT-containing serum reduced the protein level of α-SMA (P<0.01) and enhanced the gene and protein levels of Nrf2 in the nucleus and GCLC, HO-1, Keap1, GCLM, and NQO1 in the cytoplasm of HSCT6 cells (P<0.05, P<0.01). After the Nrf2 gene level of HSCT6 cells was knocked down by siRNA transfection, the protein level of α-SMA was increased (P<0.01), and the levels of GCLC, GCLM, Keap1, NQO1, and HO-1 were decreased (P<0.05, P<0.01). These results indicated that GDFMT-containing serum successfully triggered the Nrf2 signaling pathway of HSCT6 cells. ConclusionThe anti-hepatic fibrosis effect of 10%GDFMT was equivalent to that of penicillamine. In addition, GDFMT can inhibit HSC activation and reduce oxidative stress damage by activating the Nrf2/antioxidant response element (ARE) pathway, as manifested by the up-regulated expression of Nrf2 and downstream antioxidant genes (GCLC, GCLM, HO-1, Keap1, and NQO1) and reduced secretion of ROS, α-SMA, and ColⅠ.
9.Investigation of use of disposable and reuseable supplies for prevention and control of infections in Shanghai
Meixia WANG ; Jiabing LIN ; Wei SUN ; Qingfeng SHI ; Hongfei MI ; Bijie HU ; Jue PAN ; Xiaodong GAO
Chinese Journal of Nosocomiology 2025;35(17):2681-2684
OBJECTIVE To investigate the use of common disposable and reusable supplies for prevention and con-trol of infections in Shanghai.METHODS A survey was conducted for the use and reuse of disposable high-value consumables,disposable bronchoscopes and environmental cleaning and disinfection tools in Shanghai by using structured questionnaire.RESULTS Totally 81 medical institutions were involved in the survey,44(54.32%)of which were tertiary hospitals,and the median number of beds was 500.The orthopedic implants(70.37%),ul-trasound knife(69.14%)and endoscopic puncture instrument(66.67%)were the high-value consumables rank-ing the top 3 utilization rates.There was reuse of 18 types of high-value consumables in total among the 12 medi-cal institutions.The major causes of reuse of high-value consumables included fee less tan cost of consumables(58.33%)or being unable to included in charge items(33.33%).27.78%of the recycle high-value consumables were not treated with a dedicated disinfection and sterilization system and procedures for the disposable high-value consumables,and 33.33%did not have the report systems for related adverse reactions.49.09%of the medi-cal institutions reported to use the disposable bronchoscopes,4 of which reused them.The majority of the medi-cal institutions could carry out centralized cleaning and disinfection for the recycled floor cloths(60.81%)and cloth towels(56.76%),and 32.43%of the medical institutions reused the cloth towels by manual cleaning.The utilization rate of antiseptic wipes was 75.41%in adult intensive care unit,62.50%in neonatal intensive care unit.CONCLUSION The study reveals that there are some problems in the use of disposal and reusable supplies for prevention and control of infections,which may provide baseline data for management of the related supplies and the surveillance of disinfection of the recycled supplies so as to enhance the quality of management of hospital-asso-ciated infections.
10.Mechanism of baicalin in alleviating intestinal mucosal barrier injury via VDR/Nrf2/HO-1 signaling pathway in rats with intraperitoneal infection-induced sepsis
Haohao CAO ; Xiaoxia ZHANG ; Tao LIU ; Tao YANG ; Meixia XU
Chinese Journal of Nosocomiology 2025;35(15):2248-2252
OBJECTIVE To investigate the mechanism of baicalin in alleviating the intestinal mucosal barrier injury in rats with intraperitoneal infection-induced sepsis through the vitamin D receptor(VDR)/nuclear factor E2-relat-ed factor 2(Nrf2)/haemoglobin oxygenase-1(HO-1)signalling pathway.METHODS Twenty-four SD rats were randomly divided into a sham-surgery group,a model group,an ulinastatin group and a baicalin group,with six rats in each group.Sepsis models were established via cecal ligation and puncture(CLP)in rats in each groups ex-cept for the sham surgery group.Six hours after modeling,the sham-surgery and the model groups received intra-peritoneal saline,while the ulinastatin and baicalin groups were administered ulinastatin at 20,000 U/kg and ba-icalin at 100 mg/kg,respectively,via intraperitoneal injection once daily for 5 consecutive days.The histopatho-logical changes in the ileum tissue of rats in each group were observed,and the levels of oxidative stress,inflam-matory factors,and the expression of related mRNA and proteins in the VDR/Nrf2/HO-1 signalling pathway were compared.RESULTS Compared with the sham-surgery group,the model group showed disordered villus ar-rangement,severe intestinal mucosal atrophy and inflammatory cell infiltration,with necrotic epithelial cell shed-ding.Additionally,in the model group,the total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and glutathione peroxidase(GSH-PX)levels reduced,while the levels of tumor necrosis factor-α(TNF-α),inter-leukin(IL)-6,and IL-1βsignificantly increased,and the expression of VDR mRNA,Nrf2 mRNA,HO-1 mR-NA,and VDR,Nrf2,and HO-1 proteins were downregulated(P<0.05).Compared with the model group,the ulinastatin group and the baicalin group showed that villus arrangement,intestinal mucosal atrophy and inflamma-tory cell infiltration got improved,the levels of T-AOC,SOD,and GSH-PX elevated,the levels of TNF-α,IL-6,and IL-1βdecreased,and expressions of VDR mRNA,Nrf2 mRNA,HO-1 mRNA,and VDR,Nrf2,and HO-1 proteins were upregulated.Moreover,all indicators in the baicalin group were superior to those in the ulinastatin group(P<0.05).CONCLUSION Baicalin can inhibit the expression of inflammatory factors and regulate the bal-ance of oxidative stress in vivo by up-regulating the VDR/Nrf2/HO-1 signaling pathway,thereby alleviate the in-testinal mucosal barrier dysfunction caused by intraperitoneal infection-induced sepsis.

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